DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Status of the Claims
Claims 14 and 16 have been amended. Claims 1-10 and 21-24 have been canceled. Claims 11-20 and 25-34 are pending and examined herein.
Priority
This application, 18/699,169, filed 04/05/2024, is a 371 of PCT/IB2022/059507 filed on 10/05/2022, and claims benefit of REPUBLIC OF SOUTH AFRICA application ZA2021/07508 filed on 10/06/2021. This priority is acknowledged and the claims examined herein are treated as having an effective filing date of 10/06/2021.
Information Disclosure Statement
The Information Disclosure Statement filed on 04/05/2024 is acknowledged and has been considered.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
Such claim limitation(s) is/are: “…a means for receiving a biological sample…” in claim 11. Also, “…measuring means for measuring…” in claim 16. Additionally, “…means for obtaining or receiving a biological sample…”, recited in claim 17.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
The specification does not disclose or describe in a way that one of ordinary skill in the art will understand what structure, material or acts the inventor has identified to perform the recited function of “means for measuring” as there are several potential corresponding structures, material, or acts and equivalents, making the linkage to the function unclear.
The specification does not define corresponding structure, material, or acts and equivalents, for performing the recited function of “obtaining or receiving” a biological sample. While the specification recites a structure capable of receiving a biological sample from the subject, namely, “a loading or receiving area onto or into which the sample is placed” (page 7, lines 35-36), it does not define a corresponding structure capable of obtaining a biological sample.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 16 and 17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 16 and 17, the claim limitations “…measuring means for measuring…” and “…means for obtaining or receiving a biological sample…”, respectively, invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function.
Claim 16 recites a “…measuring means for measuring…”. The claims are indefinite because it is unclear of what structure or act is being linked to the measuring function based on the claim language provided. For example, the means for measuring could be interpreted as the capture agents that bind to the analyte and generate a signal, or the biosensor comprising a transducer element which converts the biological signal to an electronic signal, or an ELISA or the Luminex multiplex immunoassay platform recites in the examples.
Claim 17 recites a “…means for obtaining or receiving a biological sample…”. The specification does not define corresponding structure, material, or acts and equivalents, for performing the recited function of obtaining a biological sample. The specification merely recites the function and does not identify any specific structure to obtain a biological sample.
Therefore, the claims are indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 20 and 25-34 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Claim 20 recites “A method of diagnosing a human subject as having TB and treating the subject, the method comprising the steps of: testing a biological sample from a subject suspected of having TB for the presence of CC4 and at least one other biomarker selected from the group consisting of CC4b, procalcitonin, CCL1, apolipoprotein-CIII, RANTES and TNF-a; determining whether the subject has TB based on the detection of the biomarkers in the sample; and administering an effective amount of TB treatment to the subject.”.
The claims are directed to judicial exceptions, mainly they are abstract ideas, specifically, mental processes that can be performed in the human mind, and/or are merely observing naturally occurring correlations (laws of nature/natural correlation). These judicial exceptions are not integrated into a practical application because there is no practical application recited in the claims such as performing a treatment in a way that is particular, and not merely instructions to "apply" the exception in a generic way. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional steps amount to mere data gathering that does not go beyond well-understood, routine, and conventional activity; as detailed below.
Step 1 – Whether a claim is to a statutory category - YES
The instantly claimed invention is directed to method of diagnosing a human subject as having TB and treating the subject. The methods measure several biomarkers in a sample to determine if a subject has TB, and then administering an effective amount of TB treatment to the subject. Therefore, the instantly claimed invention falls into one of the four statutory categories.
Step 2A Prong 1 – Whether the claim is directed to a judicial exception (i.e. Does the claim recite an abstract idea, law of nature, or natural phenomenon?) - YES
Claim 20 recites the following steps which fall under mental processes grouping of abstract ideas and/or laws of nature/natural correlation:
Claim 20 discloses a method of diagnosing a human subject as having TB and treating the subject, by measuring several biomarkers in a biological sample and then using the detection of the biomarkers in the sample for “determining” whether the subject has TB.
These limitations recite a law of nature which is a judicial exception, because it is merely observing the correlation between naturally occurring biomarkers (CC4, procalcitonin, CCL1, apolipoprotein-CIII, RANTES and TNF-a) and its relationship to a disease/disease state (TB), and using these levels to make a determination of a subjects’ disease state, which are abstract ideas, specifically, abstract mental processes. Additionally, some claims recite comparison steps. In claim 33, the measured level of two biomarkers in a sample is compared to a threshold level of a biomarker to indicate TB. These comparison steps also represent abstract ideas, specifically, abstract mental processes.
The “determining” steps can be regarded as a law of nature, namely, the naturally occurring correlation between biomarker presence/level and disease state (TB). Regarding the identification of a correlation between the presence of a biomarker in a bodily sample and disease state the courts have held similar claims to be laws of nature and/or natural phenomena, as in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017) which involved claims to simply instruct a user to apply a natural law, by correlating naturally occurring enzyme levels with disease risk. In Mayo, the Supreme Court found that a claim was directed to a natural law, where the claim required administering a drug and determining the levels of a metabolite following administration, where the level of metabolite was indicative of a need to increase or decrease the dosage of the drug. See Mayo Collaborative Services V. Prometheus Labs., Inc., 566 U.S. 66, 74 (2012). The instant claims are similar to those in Mayo as they involve a "relation itself [which] exists in principle apart from any human action" (id. at 77). The instant claims do not recite administering a specific treatment (discussed further below).
Regarding the steps in claim 33 reciting a comparison of biomarkers in a sample to a threshold level of the biomarkers to indicate TB, the courts have held similar claims to be abstract mental processes, as in University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014) which involved claims to "comparing BRCA sequences and determining the existence of alterations," where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind. The claims are also similar to that in Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1067, 100 USPQ2d 1492, 1500 (Fed. Cir. 2011), which involved a claim to “collecting and comparing known information” (both of these court cases are discussed in MPEP 2106.04(a)(2) (II)(A)). The step of “determining” also constitutes an abstract mental process, involving assessing the detection of the biomarkers in the sample, and then making an evaluation or judgment as to the severity/state of a test subjects’ particular disease (TB) based on that detection. The comparison and “determining” steps could be performed in the human mind, or by a human using pen and paper, insofar as it reads on comparing levels and drawing conclusions from this about the health status of a subject.
Thus, claims 20 and 25-34 fall into a judicial exception.
Step 2A: Prong 2 - Does the claim recite additional elements that integrate the judicial exception into a practical application? The Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception.
Claims 20 and 25-34 do not recite any additional element that integrate the exception into a practical application of the exception. The additional step in claim 20 of administering an effective amount of TB treatment to the subject, is insufficient to integrate the exception into a practical application because the purpose is merely to obtain data and/or merely instructions to "apply" the exception in a generic way. Claim 20 does not recite a particular treatment, and as MPEP 2106.04(d)(2) states, the treatment or prophylaxis limitation must be “particular,” i.e., specifically identified so that it does not encompass all applications of the judicial exception(s), for it to integrate the judicial exception.
Regarding dependent claims 25-34, they do not recite any additional elements that integrate the judicial exception into a practical application. The additional steps of testing for the presence of several specific biomarkers (claims 25, 26, 30, and 31), diagnosing a specific type of TB (claims 27 and 34), using a specific sample type (claims 28 and 29), contacting the sample with capture agents (claim 32), and comparing the measured biomarker level to a threshold level to indicate TB (claim 33), are insufficient to integrate the exception into a practical application because the purpose is merely to obtain data to observe a naturally occurring correlation and/or perform a mental process.
As in In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989), such activity involving performing clinical tests on individuals constitutes mere data gathering, and does not go beyond insignificant extra-solution activity. See MPEP §§ MPEP 2106.04(d)(I) and 2106.05(g). There are no subsequent steps recited after the “determining” or comparison steps that would practically apply the method depending on the results of the measurements, e.g., specific treatment or other process steps that are performed after the test subject has been diagnosed with a disease.
In particular, of the claims indicated in the rejection heading, none of the additionally recited limitations amount to an additional element or combination of elements that apply, rely on, or use the judicial exceptions in a manner that impose meaningful limit on the judicial exceptions.
Step 2B; Whether the additional elements contribute an “inventive concept”. In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP 2106.05.
Briefly, claims 20 and 25-34 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because of the following reasons. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, has been found to be insufficient to add “significantly more” (MPEP 2106.05(I)(A)).
The additional steps recited above do not add a meaningful limitation to the instant method as they would have been routinely used by those of ordinary skill in the art as supported by Chegou et al. (WO2019224755A1), (herein referred to as Chegou), Jacobs et al. (2016). “Identification of novel host biomarkers in plasma as candidates for the immunodiagnosis of tuberculosis disease and monitoring of tuberculosis treatment response”. Oncotarget, 7(36), 57581, (herein referred to as Jacobs), Patil et al. (2015). “Serum and CSF cytokines and matrix metalloproteinases in spinal tuberculosis”. Inflammation Research, 64(2), 97-106, (herein referred to as Patil).
Chegou teaches methods, devices, kits and computer-implemented methods for diagnosing (and optionally treating) tuberculous meningitis (TBM) (abstract). Chegou teaches that in embodiment of the invention, there is provided a device for diagnosing tuberculous meningitis (TBM), the device comprising a means for receiving a cerebrospinal fluid (CSF) sample from a subject suspected of having TBM (page 3, lines 29-32). Chegou teaches that the method may also comprise testing the cerebrospinal fluid (CSF) sample for one or more additional biomarkers selected from the group consisting of l-309 (CCL1), CCL5 (RANTES), tumour necrosis factor (TNF)-a, CC4, CC4b, Apo Clll, apolipoprotein (Apo)-A1, CC5, TGF-a, CC3, MIP- 1a (CCL3), and MCP-1 (CCL2) (page 3, lines 4-16). Chegou teaches that a capture agent may be used to bind each of the biomarkers (page 3, lines 20).
Jacobs teaches the identification of novel host biomarkers in plasma as candidates for the immunodiagnosis of tuberculosis disease and monitoring of tuberculosis treatment response (title). Jacobs teaches that there is an urgent need for new tools for the rapid diagnosis of tuberculosis disease, and that they evaluated the potentials of 74 host markers as biomarkers for the immunological diagnosis of tuberculosis and monitoring of treatment response (abstract). Jacobs teaches that concentrations of biomarkers were investigated in plasma samples from all the study participants using Luminex multiplex immunoassay, and the experiments were performed blindly, according to the instructions of the kit manufacturers, on the Bio-Plex platform (page 57589, column 1, 4th paragraph). Jacobs teaches that the median levels of CRP, SAP, procalcitonin (PCT), ferritin, TPA, SAA, ADAMTS-13, p-selectin, GDF-15, I-309, IFN-γ, IP-10, TNF-α, CFH, MIG, ITAC, HCC-1 and MIP-4 were significantly higher in TB cases (page 57582, column 2, 2nd paragraph).
Patil teaches the measurement of serum and CSF cytokines and matrix metalloproteinases in spinal tuberculosis (title). Patil teaches that they enrolled 55 histopathologically/microbiologically confirmed patients with spinal tuberculosis, and also included 55 control subjects (abstract – Materials and Methods). Patil teaches that blood and cerebrospinal fluid (CSF) were collected both from cases and controls, and that tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL-6, IL-8, IL-10, matrix metalloproteinases MMP-2 and MMP-9 were measured by enzyme-linked immunosorbent assay (ELISA) (abstract – Materials and Methods). Patil teaches that serum and CSF cytokines and MMPs were significantly higher in patients with spinal tuberculosis than in controls (abstract -Results). Patil teaches that about 10–35 % cases of extrapulmonary tuberculosis involve the bones and joints, and that spinal tuberculosis accounts for about 50 % cases of skeletal tuberculosis (page 98, column 1, 1st paragraph). Patil teaches that similar to pulmonary tuberculosis, the expression of cytokines and MMPs may play a significant role in the pathogenesis of spinal tuberculosis (page 98, column 1, 3rd paragraph).
For all of these reasons, the claims fail to include additional elements that are sufficient to amount to significantly more than the judicial exception(s). Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to a law of nature and abstract idea without significantly more. For additional guidance, applicant is directed generally to MPEP § 2106.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 11, 13-17, 19, 20, 25-29, 31-33 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chegou et al. (WO2019224755A1), (herein referred to as Chegou).
Regarding claims 11, 13, 20, 25, 26, and 31, Chegou teaches methods, devices, kits and computer-implemented methods for diagnosing (and optionally treating) tuberculous meningitis (TBM) (abstract). Chegou teaches that in embodiment of the invention, there is provided a device for diagnosing tuberculous meningitis (TBM), the device comprising a means for receiving a cerebrospinal fluid (CSF) sample from a subject suspected of having TBM (page 3, lines 29-32). Chegou teaches that the method may also comprise testing the cerebrospinal fluid (CSF) sample for one or more additional biomarkers selected from the group consisting of l-309 (CCL1), CCL5 (RANTES), tumour necrosis factor (TNF)-a, CC4, CC4b, Apo Clll, apolipoprotein (Apo)-A1, CC5, TGF-a, CC3, MIP- 1a (CCL3), and MCP-1 (CCL2) (page 3, lines 4-16). Chegou teaches that a capture agent may be used to bind each of the biomarkers (page 3, lines 20). Chegou teaches that one or more indicators may be provided to indicate when binding of each of the capture agents and biomarkers occurs, and that detection of one or more of the biomarkers in the sample or a measured signal which equates to a level of biomarker in the sample which is higher than a threshold level of the same biomarker may be an indicator of TBM (page 3, lines 20-27). Chegou teaches determining whether the subject has TBM based on the detection of the biomarkers in the sample; and administering an effective amount of TBM treatment to the subject if the subject is in need thereof (page 7, lines 23-26).
Regarding claims 14 and 15, Chegou teaches that the capture agents may be selected from the group consisting of antibodies, affybodies, ankyrin repeat proteins, armadillo repeat proteins, nucleic acid aptamers, peptides, carbohydrate ligands, synthetic ligands and synthetic polymers (page 4, lines 7-9). Chegou teaches that preferably, the capture agents are antibodies (page 4, lines 9-10).
Regarding claim 16, Chegou teaches that the device may further include measuring means for measuring the levels of the detected biomarkers. (page 7, lines 1-2).
Regarding claims 17 and 19, Chegou teaches a kit can also be provided to enable the method of the invention to be performed, and that the kit could include one or more of the following: capture agents, such as antibodies, for binding the intended biomarkers (see biomarkers above); a means for obtaining or receiving a CSF or blood sample from a subject; a point-of-care device as described above; and/or instructions, in electronic or paper form, for performing the method (page 12, lines 10-15).
Regarding claims 27-29, Chegou teaches that the method for diagnosing (and optionally treating) tuberculous meningitis (TBM) may also comprise testing the cerebrospinal fluid (CSF) sample for one or more additional biomarkers (page 3, lines 4-16).
Regarding claim 32 and 33, Chegou teaches that a capture agent may be used to bind each of the biomarkers (page 3, lines 20). Chegou teaches that one or more indicators may be provided to indicate when binding of each of the capture agents and biomarkers occurs, and that detection of one or more of the biomarkers in the sample or a measured signal which equates to a level of biomarker in the sample which is higher than a threshold level of the same biomarker may be an indicator of TBM (page 3, lines 20-27).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 12, 18, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Chegou as applied to claim 11 and 17 above, in view of Jacobs et al. (2016). “Identification of novel host biomarkers in plasma as candidates for the immunodiagnosis of tuberculosis disease and monitoring of tuberculosis treatment response”. Oncotarget, 7(36), 57581, (herein referred to as Jacobs).
The teachings of Chegou are incorporated herein.
Regarding claims 12, 18, and 30, Chegou teaches all the limitations of claims 11 and 17 of the instant application, as well as the capture agents for binding and testing for the presence of CC4, CC4b, and CCL1.
However, Chegou does not teach the capture agents for binding and testing for the presence of procalcitonin.
Jacobs teaches the identification of novel host biomarkers in plasma as candidates for the immunodiagnosis of tuberculosis disease and monitoring of tuberculosis treatment response (title). Jacobs teaches that there is an urgent need for new tools for the rapid diagnosis of tuberculosis disease, and that they evaluated the potentials of 74 host markers as biomarkers for the immunological diagnosis of tuberculosis and monitoring of treatment response (abstract). Jacobs teaches that concentrations of biomarkers were investigated in plasma samples from all the study participants using Luminex multiplex immunoassay, and the experiments were performed blindly, according to the instructions of the kit manufacturers, on the Bio-Plex platform (page 57589, column 1, 4th paragraph). Jacobs teaches that the median levels of CRP, SAP, procalcitonin (PCT), ferritin, TPA, SAA, ADAMTS-13, p-selectin, GDF-15, I-309, IFN-γ, IP-10, TNF-α, CFH, MIG, ITAC, HCC-1 and MIP-4 were significantly higher in TB cases (page 57582, column 2, 2nd paragraph).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the kit for diagnosing TB as taught by Chegou, to include a capture agent for binding procalcitonin, as taught by Jacobs, as a matter of simple substitution. The aim of the device and kit taught by Chegou is to diagnose TB by measuring biomarkers from a biological sample, and Jacobs teaches that procalcitonin acts as a biomarker of TB, and also teaches the measurement of several of the same biomarkers as Chegou such as CC4, CCL1, and TNF-a (Table 2). Therefore, it would have been a matter of simple substitution to replace one of the capture agents for a biomarker measured by Chegou, with a capture reagent for procalcitonin to improve the diagnostic potential/accuracy of the device and method taught by Chegou, in order to improve patient outcomes with early diagnosis. Additionally, a person of ordinary skill in the art would be motivated to make this modification Jacobs teaches that there is an urgent need for new tools for the rapid diagnosis of tuberculosis disease. A person of ordinary skill would have had a reasonable expectation of success in modifying the device/kit of Chegou, because Jacobs teaches the use of commercially available capture reagents/kit to measure procalcitonin, and both references are in the same field of endeavor of measuring biomarkers for TB diagnosis.
Claim 34 is rejected under 35 U.S.C. 103 as being unpatentable over Chegou as applied to claim 20 above, in view of Patil et al. (2015). “Serum and CSF cytokines and matrix metalloproteinases in spinal tuberculosis”. Inflammation Research, 64(2), 97-106, (herein referred to as Patil).
The teachings of Chegou are incorporated herein.
Regarding claim 34, Chegou teaches all the limitations of claim 20 of the instant application, but does not teach that the TB is spinal TB.
Patil teaches the measurement of serum and CSF cytokines and matrix metalloproteinases in spinal tuberculosis (title). Patil teaches that they enrolled 55 histopathologically/microbiologically confirmed patients with spinal tuberculosis, and also included 55 control subjects (abstract – Materials and Methods). Patil teaches that blood and cerebrospinal fluid (CSF) were collected both from cases and controls, and that tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL-6, IL-8, IL-10, matrix metalloproteinases MMP-2 and MMP-9 were measured by enzyme-linked immunosorbent assay (ELISA) (abstract – Materials and Methods). Patil teaches that serum and CSF cytokines and MMPs were significantly higher in patients with spinal tuberculosis than in controls (abstract -Results). Patil teaches that about 10–35 % cases of extrapulmonary tuberculosis involve the bones and joints, and that spinal tuberculosis accounts for about 50 % cases of skeletal tuberculosis (page 98, column 1, 1st paragraph). Patil teaches that similar to pulmonary tuberculosis, the expression of cytokines and MMPs may play a significant role in the pathogenesis of spinal tuberculosis (page 98, column 1, 3rd paragraph).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method for diagnosing and treating TB patients as taught by Chegou, to instead investigate spinal TB, as taught by Jacobs, as a matter of simple substitution. The focus of both Chegou and Patil is the measurement of TB biomarkers in a biological sample, and both already teach the measurement of several of the same biomarkers as such as TNF-a, IFN, IL-6, and IL-8, with both references using CSF as the samples. Therefore, it would have been a matter of simple substitution to apply the method of diagnosing and treating a TB subject as taught by Chegou, specifically to spinal TB patients as Patil teaches that spinal tuberculosis exhibits cytokine patterns similar to other forms of tuberculosis. A person of ordinary skill in the art would be motivated to make this modification in order to improve spinal TB diagnostics/prognostics in order more effectively diagnose and monitor treatment responses to improve patient outcomes. A person of ordinary skill would have had a reasonable expectation of success in modifying the method of Chegou, because it would merely require applying the same teachings of Chegou to a different population of patients that instead have spinal TB specifically, as there are no barriers or limitations because both Chegou and Patil measured biomarkers in CSF.
Conclusion
For all the reasons discussed above, claims 11-20 and 25-34 are rejected and therefore no claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER JOSEPH HOFFMAN whose telephone number is (571)272-9080. The examiner can normally be reached 10:00-6:30 M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALEXANDER J. HOFFMAN/ Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/ Supervisory Patent Examiner, Art Unit 1677 September 16, 2026
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